| abstract |
The invention relates to aprotinin variants with a net charge of +3 to -3 at pH 7. In the binding site, the amino acid radical 10 is Ser, the amino acid radical 13 is Ile, Phe or Leu, the amino acid radical 15 is Arg, the amino acid radical 17 is Tyr, Leu or Arg, and the amino acid radical 19 is Thr or Lys. The invention also relates to bikunins, comprising two aprotinin variants linked by a spacer with several amino acid radicals. One of said aprotinin variants is a) an aprotinin variant wherein the amino acid radical 13 is Ile, Phe or Leu, the amino acid radical 15 is Arg, Val or Leu, the amino acid radical 17 is Tyr, Leu or Ala, the amino acid radical 19 is Thr or Lys, the amino acid radical 39 is Arg or Leu, and the amino acid radical 46 is Leu or Lys; or b) an inventive aprotinin variant as defined above. The invention also relates to medicaments containing one or several of said aprotinin variants or bikunins, DNA sequences which give the coding for one of said aprotinin variants or bikunins, micro-organisms containing a DNA sequence of this type, and a method for producing said aprotinin variants and bikunins using micro-organisms. |